The mission of the High-Throughput Screening and Chemical Library (HTSCL) Core is to support the high-throughput screening, medicinal chemistry, automated microscopy and image analysis needs of the individual Projects. The Burnham Institute for Medical Research (BIMR) has collaborated with neighboring academic institutions to establish the San Diego Center for Chemical Genomics (SDCCG). The SDCCG will provide the projects access to state-of-the-art robotics and instrumentation for HTS for the purpose of discovering novel therapeutics for Parkinson's disease (PD), which will be a major function of Core E. HTS will be conducted in vitro against biochemical targets or cellular responses (Projects 2 3, and 4). A second major function of the core will be the automated acquisition and analysis of images of cells to quantify marker or phenotypic responses (Projects 2 and 3) using the sophisticated and proprietary automated microscopy platforms and algorithms developed within the center. In addition, the core will assume the responsibility of converting primary validated hits to leads through medicinal chemistry and nuclear magnetic resonance (NMR)-based and computational modeling strategies for compound optimization (Projects 2, 3, and 4). Core E will provide these functions for the Parkinson's Disease (PD) researchers in this Center.